The long-term goal of our research program is to understand the process of selective gene activation in molecular terms using Drosophila as a model system. The specific objectives of this grant are to explore questions of reversibility in the alterations of chromatin structure that occur during gene activation. The changes in chromatin structure are detected by changes in the pattern of DNA fragments generated by nuclease digestion. Studies with the heat shock genes, which can be turned on and off in all Drosophila cells, indicate that for these genes the changes are reversible both in embryonic cells and in terminally differentiated cells. Work on a "housekeeping" gene, a gene encoding one of the ribosomal proteins, is being initiated. We are working to obtain a recombinant DNA clone for a gene induced by ecdysterone in a tissue culture cell line in order to carry out such studies on this type of locus. Most genes are turned off by heat shock. Consequently it should be possible to study all three gene types in an "on" and in an "off" configuration, both in Drosophila cells in continuous culture and in the cells caused by ecdysterone to terminally differentiate.